Dendritic cells (DC), first described by Steinman and Cohn, Z. A. J. Exp. Med. 137: 1142, 1973 are the most potent antigen presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T cell dependent antibodies. They differentiate from their precursors into so-called “immature” DCs which are present in most tissues (Banchereau, J. and Steinman, R. M. Nature 392: 245, 1998). The best characterized immature DCs is the Langerhans cells (LC), located above the basal layer of epithelial cells of the skin. Until recently, it was difficult to isolate dendritic cells or Langerhans cells (Steinman, R. M., Lustig, D. S. and Cohn, Z. A. J. Exp. Med. 139: 1431, 1974). Our knowledge on these important antigen presenting cells has increased dramatically because of success in culturing these cells in vitro. Granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) favours the outgrowth of dendritic cells from CD14+ blood monocytes and CD34+ cord blood stem cells (Palucka, K. A. Taquet, N. Sanchezchapuis, F. and Gluckman, J. C. J. Immunol. 160: 4587, 1998). On the other hand, transforming growth factor β1 (TGF β1) and IL-4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells (Geissmann, F. C., Prost, J., Monnet, M., Dy, M., Browsse, N. and Hermine, O. J. Exp. Med. 187: 961, 1998). Culturing purified cord blood CD34+ cells with GM-CSF and tumor necrosis factor α (TNF-α) also leads to dendritic Langerhans cells (Caux, C., Dezutter-Dambuyant, C., Schmitt, D. and Banchereau, J. Nature 360: 258, 1992).
Several studies have shown that in vitro grown dendritic cells or dendritic Langerhans cells can be used in active, specific vaccination schemes to generate protective immunity in several tumour models (Young, J. W. and Inaba, K. J. Exp. Med. 187: 7, 1996). (Chakraborty, N. G., Li, L., Sporn, J. R., Kurtzman, S. H., Ergin, M. T. and Mukheji, B. J. Immunol. 162: 5576, 1991; Hsu, F. J., Benike, C., Fagnoni, F., Liles, T. M., Czerwinski, D., Taidi, B., Engleman, E. G. and Ltry, R. Nature Medicine 2: 52, 1996). Controlled studies confirmed the immunogenecity of in vitro grown DCs in human, and demonstrated that a single injection of mature DCs rapidly expands T cell immunity (Dhodapkar, M. V., Steinman, R. M., Sapp, M., Desai, H., Fossella, C., Krasrvsky, J., Donahoe, S. M., Dunbar, P. R., Cerundolo, V., Nixon, D. F. and Bhardwaj, N. J. Clin. Invest. 104: 173, 1999).
Evidences are being accumulated on the potential of dendritic Langerhans cells in enhancing organ transplant survival. Graft hyporeactivity induced by donor derived dendritic cell progenitors has been reported in animal model (Hirano, A., Fraser, M. O., Jordan, M. L., Takayama, T., Lu, L. and Thomson, A. W. Transplant Proc. 32: 260, 2000). This is associated with microchiemerism and growth of donor dendritic cell progenitors in recipient bone marrow (Khanna, A., Steptae, R. J., Antonysamy, M. A., Li, S. and Thomson, A. W. Transplantation 65: 479, 1998).